A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABI-H3733 in Healthy Adults

Sponsor

Assembly Biosciences (Industry)

Overall Status

Completed

CT.gov ID

NCT04271592

Collaborator

(none)

120

Enrollment

Location

Arms

Actual Duration (Months)

15.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is designed to assess safety, tolerability, pharmacokinetics (PK), formulation (liquid and solid oral forms) and food effect of ABI-H3733 in healthy participants. Part 1 includes evaluation of the safety, tolerability, and PK of ABI-H3733 during single ascending dose (SAD) and multiple-ascending dose (MAD) administration of the oral liquid formulation. Part 2 includes assessment of a solid dosage formulation of ABI-H3733 in participants under fasted conditions or after a high-fat meal. Optional cohorts may be enrolled in Parts 1 and 2 of the study to explore additional dose levels, solid oral dosage formulations, or for cohort expansion.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis B	Drug: ABI-H3733 Liquid Oral Dosage Form Drug: ABI-H3733 Solid Oral Dosage Form Drug: Placebo to ABI-H3733 Liquid Oral Dosage Form Drug: Placebo to ABI-H3733 Solid Oral Dosage Form	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase 1, Randomized, Blinded, Placebo-Controlled, Single and Multiple Dose Escalation and Food Effect Study of ABI-H3733 in Healthy Subjects

Actual Study Start Date :

May 17, 2020

Actual Primary Completion Date :

Nov 3, 2020

Actual Study Completion Date :

Jan 14, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1: SAD Cohorts 1-7 ABI-H3733 Liquid Form A single dose of ABI-H3733 liquid oral dosage form administered on Day 1. Cohort 1 will receive a 100-mg dose. Subsequent cohorts 2-7 will receive a ≤3-fold increase in dose from the previous cohort; the dose will be determined by evaluation of safety and PK data from previous cohorts.	Drug: ABI-H3733 Liquid Oral Dosage Form ABI-H3733 liquid oral dosage form
Placebo Comparator: Part 1: SAD Cohorts 1-7 Placebo Liquid Form A single dose of placebo matching ABI-H3733 liquid oral dosage form will be administered on Day 1. Cohort 1 will receive a 100-mg dose. Subsequent cohorts 2-7 will receive a ≤3-fold increase in dose from the previous cohort; the dose will be determined by evaluation of safety and PK data from previous cohorts.	Drug: Placebo to ABI-H3733 Liquid Oral Dosage Form Placebo to ABI-H3733 liquid oral dosage form
Experimental: Part 1: MAD Cohorts 8-10 ABI-H3733 Liquid Form Once-daily doses of ABI-H3733 liquid oral dosage form will be administered from Day 1 to Day 5. Cohort 8 will receive a dose determined from evaluation of the data from the SAD cohorts. Subsequent cohorts 9 and 10 will receive a ≤3-fold increase in dose from the previous cohort; the dose will be determined by evaluation of safety and PK data from previous cohorts.	Drug: ABI-H3733 Liquid Oral Dosage Form ABI-H3733 liquid oral dosage form
Placebo Comparator: Part 1: MAD Cohorts 8-10 Placebo Liquid Form Once-daily doses of placebo matching ABI-H3733 liquid oral dosage form will be administered from Day 1 to Day 5. Cohort 8 will receive a dose determined from evaluation of the data from the SAD cohorts. Subsequent cohorts 9 and 10 will receive a ≤3-fold increase in dose from the previous cohort; the dose will be determined by evaluation of safety and PK data from previous cohorts.	Drug: Placebo to ABI-H3733 Liquid Oral Dosage Form Placebo to ABI-H3733 liquid oral dosage form
Experimental: Part 2: Single Dose Fasted Cohort 11 ABI-H3733 Solid Form A single dose of ABI-H3733 solid oral dosage form will be administered in a fasted state on Day 1. The decision to proceed with Part 2 and the dose administered will be determined after evaluation of cumulative safety and PK data from Part 1.	Drug: ABI-H3733 Solid Oral Dosage Form ABI-H3733 solid oral dosage form
Placebo Comparator: Part 2: Single Dose Fasted Cohort 11 Placebo Solid Form A single dose of placebo matching ABI-H3733 liquid oral dosage form will be administered in a fasted state on Day 1. The decision to proceed with Part 2 and the dose administered will be determined after evaluation of cumulative safety and PK data from Part 1.	Drug: Placebo to ABI-H3733 Solid Oral Dosage Form Placebo to ABI-H3733 solid oral dosage form
Experimental: Part 2: Single Dose Fed Cohort 12 ABI-H3733 Solid Form A single dose of ABI-H3733 solid oral dosage form will be administered after a high-fat meal on Day 1. The decision to proceed with Part 2 and the dose administered will be determined after evaluation of cumulative safety and PK data from Part 1.	Drug: ABI-H3733 Solid Oral Dosage Form ABI-H3733 solid oral dosage form
Placebo Comparator: Part 2: Single Dose Fed Cohort 12 Placebo Solid Form A single dose of placebo matching ABI-H3733 solid oral dosage form will be administered after a high-fat meal on Day 1. The decision to proceed with Part 2 and the dose administered will be determined after evaluation of cumulative safety and PK data from Part 1.	Drug: Placebo to ABI-H3733 Solid Oral Dosage Form Placebo to ABI-H3733 solid oral dosage form

Outcome Measures

Primary Outcome Measures

Number of Participants with One or More Adverse Events [Up to Day 10]
Number of Participants with One or More Related Adverse Events [Up to Day 10]
Number of Participants with One or More Severe (Grade ≥3) Adverse Events [Up to Day 10]

Secondary Outcome Measures

SAD Cohorts 1-7: Area Under the Plasma Concentration Time Curve (AUC) of ABI-H3733 [before and at pre-specified time points up to 120 hours after dosing]
SAD Cohorts 1-7: Maximum Plasma Concentration (Cmax) ABI-H3733 [before and at pre-specified time points up to 120 hours after dosing]
SAD Cohorts 1-7: Time of Cmax (Tmax) of ABI-H3733 [before and at pre-specified time points up to 120 hours after dosing]
SAD Cohorts 1-7: Apparent Terminal Elimination Half-life (t1/2) of ABI-H3733 [before and at pre-specified time points up to 120 hours after dosing]
SAD Cohorts 1-7: Apparent Systemic Clearance (CL/F) of ABI-H3733 [before and at pre-specified time points up to 120 hours after dosing]
SAD Cohorts 1-7: Apparent Volume of Distribution (Vz/F) of ABI-H3733 [before and at pre-specified time points up to 120 hours after dosing]
MAD Cohorts 8-10: AUC of ABI-H3733 [before and at pre-specified time points up to 24 hours after dosing on Day 1; before and up to 120 hours after dosing on Day 5]
MAD Cohorts 8-10: Cmax Over the Dosing Interval of ABI-H3733 [before and at pre-specified time points up to 24 hours after dosing on Day 1; before and up to 120 hours after dosing on Day 5]
MAD Cohorts 8-10: Tmax of ABI-H3733 [before and at pre-specified time points up to 24 hours after dosing on Day 1; before and up to 120 hours after dosing on Day 5]
MAD Cohorts 8-10: t1/2 of ABI-H3733 [before and at pre-specified time points up to 24 hours after dosing on Day 1; before and up to 120 hours after dosing on Day 5]
Single Dose Cohorts 11-12: AUC of ABI-H3733 [before and at pre-specified time points up to 120 hours after dosing]
Single Dose Cohorts 11-12: Cmax of ABI-H3733 [before and at pre-specified time points up to 120 hours after dosing]
Single Dose Cohorts 11-12: Tmax of ABI-H3733 [before and at pre-specified time points up to 120 hours after dosing]
Single Dose Cohorts 11-12: t1/2 of ABI-H3733 [before and at pre-specified time points up to 120 hours after dosing]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

No clinically significant abnormal findings on physical exam, medical history, or clinical laboratory results at screening.

Exclusion Criteria:

Positive test results for human immunodeficiency virus (HIV) or hepatitis B or C.
History of or current persistent drug or alcohol abuse.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Auckland Clinical Studies	Auckland		New Zealand

Sponsors and Collaborators

Assembly Biosciences

Investigators

Study Director: Katia Alves, MD, Assembly Biosciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Assembly Biosciences

ClinicalTrials.gov Identifier:

NCT04271592

Other Study ID Numbers:

ABI-H3733-101
U1111-1246-2965

First Posted:

Feb 17, 2020

Last Update Posted:

Jan 27, 2021

Last Verified:

Jan 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Additional relevant MeSH terms:

Hepatitis B

Hepatitis B, Chronic

Study Results

No Results Posted as of Jan 27, 2021